The overall objective of this proposal is to develop a center of research excellence at Harvard & Boston Universities which joins together complementary investigative and training capabilities in a clinical research facility, and in related laboratories in behavioral pharmacology and biochemistry. The research program at the Boston Center is directed toward the clarification of the nature of the addictive process through analyses of the biological, behavioral and biochemical correlates of various addictive disorders in man and in relevant animal models. l. Biobehavioral studies of opiate addiction in man are proposed which utilize the techniques of behavioral analyses developed by Mendelson and Mello in studies of alcoholics. The methodology permits the investigation of the multiple biological, physiological, and psychological parameters associated with drug-seeking and withdrawal. The technique will be expanded to explore the effects of opiate antagonists (and/or substitutes) upon a subject-determined pattern of opiate administration in the research setting. Long-term community follow-up of patients on these medications will also be explored. 2. Biobehavioral studies of models of addictive disorders in the rat will determine the relative role of a number of factors upon the learning and/or extinction of opiate-seeking behavior to orally administered solutions of etonitizene and intravenously administered morphine. These studies will focus upon environmental and pharmacological manipulations which may modify opiate reinforcement and/or alter the addiction cycle. The work is designed to complement the clinical research. 3. Studies of biogenic amines and their relationship to the addiction process and its treatment will investigate the twenty-four hour pattern of urinary excretion of biogenic amines and metabolites and daily periodic assessments of plasma levels of dopamine- b-hydroxylase (DBH) in narcotic addicts during opiate acquisition, withdrawal, and treatment. Studies in changes in brain catecholamine uptake, release and metabolism and effects on cyclic AMP in rat brain during acute and chronic morphine administration and during abstinence will complement this data.